1. Foundation for Integrated Medicine Detoxification Leo Galland M.D. Foundation for Integrated Medicine

2. OUR BODIES DETOXIFY Exogenous, foreign substances Endogenous, internally created substances

3. Foundation for Integrated Medicine ENDOGENOUS SUBSTANCES Gut toxins –bacteria –parasites –yeast Hormones Bile acids Metabolic intermediates

4. Foundation for Integrated Medicine EXOGENOUS SUBSTANCES Xenobiotics –herbicides –pesticides Air pollutants –auto exhaust –tobacco smoke Pharmaceuticals

5. Foundation for Integrated Medicine DETOXIFICATION TRANSFORMS MOLECULES Functionalization Phase I Conjugation Phase II

6. Foundation for Integrated Medicine MAJOR SITES OF ENZYMATIC DETOXIFICATION Liver –most important organ Lung, intestine, kidney & skin –demonstrable detox capability

7. Foundation for Integrated Medicine LIVER DETOXIFICATION PHASE ONE: OXYGENATION PHASE TWO: CONJUGATION

8. Foundation for Integrated Medicine PHASE ONE ENZYMES Cytochrome P450 system (20-30 enzymes) Use oxygen to alter molecules By-products include free oxygen radicals End products may be more dangerous than the initial chemicals

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10. PHASE ONE ACTIVITY Increased in tobacco smokers Increased or decreased by medications Increased by char-broiled meats and high intake of alcohol, BHT or vegetable oils Variably influenced by phytochemicals, especially flavonoids Decreased in vegans

11. Foundation for Integrated Medicine PHASE ONE INDUCERS cabbage, broccoli, brussel sprouts (indole-3-carbinol) oranges and tangerines (limonene) caraway and dill seeds (limonene)

12. Foundation for Integrated Medicine PHASE ONE INHIBITORS grapefruit (naringenin) turmeric (curcumin) capsicum (capsaicin) cloves (eugenol) onions (quercetin)

13. Foundation for Integrated Medicine ZINC DEFICIENCY DISRUPTS PHASE ONE ACTIVITY, SHIFTING ENZYME PATTERNS TO INCREASE THE PRODUCTION OF CANCER PROMOTERS

14. Foundation for Integrated Medicine PHASE TWO:CONJUGATION sulfate amino acids: glycine, taurine, glutamine, ornithine, arginine glutathione methylation glucuronic acid

15. Foundation for Integrated Medicine PHASE TWO INHIBITION nutritional deficiency toxin exposures that exhaust supplies of substrates or co-factors example: acetaminophen, alcohol and low protein intake deplete glutathione, which is needed for acetaminophen detoxification

16. Foundation for Integrated Medicine PHASE TWO STIMULATION cabbage, broccoli, cauliflower, brussel sprouts, kale (glucosinolates) garlic oil, rosemary, soy citrus peel, dill and caraway oils (limonene) curcumin S-adenosyl methionine (SAM) milk thistle (silymarins)

17. Foundation for Integrated Medicine Glucosinolates Must Be Hydrolyzed by the Enzyme Myrosinase Glucosinolates (>70 types) are separated from myrosinase in plants, not sprouts Crushing the plant before cooking liberates the active phytochemical Sulforaphane releases nuclear respiratory factor-2 (Nrf2), induces glutathione S-transferase

18. Foundation for Integrated Medicine Glucosinolates Must Be Hydrolyzed by the Enzyme Myrosinase Indole-3-carbinol is converted to diindolyl methane (DIM) by acid conjugation in the stomach DIM stimulates CYPA1/1A2, which alters estrone metabolism to reduce estrogenic activity and inhibit growth of breast cancers

19. Foundation for Integrated Medicine PHASE TWO GENETICS Genetic variation in the activity of different Phase two enzymes in the liver, brain or intestines may account for disease susceptibility: colon cancer breast cancer Parkinson’s disease

20. Foundation for Integrated Medicine ANTIOXIDANT BENEFITS protect DNA and cell or organelle membranes from free radical damage elevate levels of glutathione stimulate immune responses increase activity of tumor suppressor genes inhibit activity of enzymes needed for tumor growth

21. Foundation for Integrated Medicine ANTIOXIDANT PROTECTION vitamins E and C carotenoids (carotene, lycopene, lutein) flavonoids selenium glutathione lipoic acid

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23. PLANT FUNCTIONS OF FLAVONOIDS Production stimulated by lack of light Stress: microbes, heavy metals, ozone, sulfur dioxide, pH changes Inhibit photo-oxidation and microbial growth

24. Foundation for Integrated Medicine CLASSES OF FLAVONOIDS Glycosides –rutin, hesperidin Aglycones –flavonols (quercetin) –anthocyanidins (catechin) Proanthocyanidins –dimers, trimers of anthocyanidins Tannins –polymeric anthocyanidins

25. Foundation for Integrated Medicine FLAVONOID EFFECTS ON MAMMALIAN CELLS Potent anti-oxidants –quench free radicals –chelate transition metals Inhibit oxygenases: PG synthetase –5-lipoxygenase Alter activity of ION pumps

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31. METHYLATION protects DNA from mutation depends upon methionine (SAM), folic acid, vitamin B12 enhanced by dimethylglycine (DMG), choline, betaine CAVEAT: methylation inactivates genes; aberrant methylation may inactivate tumor suppressor genes

32. Foundation for Integrated Medicine THE INTESTINES AND DETOXIFICATION absorption and excretion of toxins second largest volume of detox enzymes intestinal toxicity stresses the liver

33. Foundation for Integrated Medicine DETOXIFYING AGENTS dietary fiber (beans, grains) antioxidants (vegetables, seeds, fruit) Phase Two inducers (crucifers) glutathione enhancers (selenium...) methylation enhancers (folic acid...) spices (turmeric, rosemary) herbs (milk thistle, Ginkgo biloba)

34. Foundation for Integrated Medicine AB, 6 year old girl with psoriasis Prior to age 3: infantile colic, rarely ill Age 3: otitis media associated with guttate psoriasis, treated with steroids and dovenex Naturopath: avoid junk food, use flax oil and primrose oil progressively worse On a 50% fruit and vegetable diet, nightshade free dramatic improvement, leaving few tiny patches on arms

35. Foundation for Integrated Medicine AB, 6 year old girl with psoriasis Her psoriasis controlling diet -Breakfast: Granola, soy milk, water -Lunch: Whole wheat bread, tuna, cheese, almond butter, fruit conserves, water -Dinner: Chicken, salmon, noodles, brown rice, salad, vegetables -Snacks: fruits and vegetables